Role of ferrous iron chelator 2,2'-dipyridyl in preventing delayed vasospasm in a primate model of subarachnoid hemorrhage.
OBJECTIVE
Oxyhemoglobin (HbO2) causes vasospasm after subarachnoid hemorrhage (SAH). The most likely spasmogenic component of HbO2 is iron. Various iron chelators, such as deferoxamine, have prevented vasospasm in vivo with limited success. However, only chelators of iron in the ferric state have been studied in animal models of vasospasm after SAH. Because free radical formation requires the ferrous (Fe++) moiety and Fe++ is a potent binder of the vasodilator nitric oxide, the authors hypothesized that iron in the ferrous state causes vasospasm and that chelators of Fe++, such as 2,2'-dipyridyl, may prevent vasospasm. This study was undertaken to investigate the influence of 2,2'-dipyridyl on vasospasm after induction of SAH in a primate model.


METHODS
Twelve cynomolgus monkeys were randomly divided into two groups and then both groups underwent placement of an arterial autologous blood clot in the subarachnoid space around the right middle cerebral artery (MCA). The five animals in the control group received intravenously administered saline and the seven treated animals received intravenously administered chelator (2,2'-dipyridyl) for 14 days. Sequential arteriography for assessment of MCA diameter was performed before and on the 7th day after SAH.


CONCLUSIONS
Prevention of cerebral vasospasm by means of treatment with continuous intravenous administration of 2,2'-dipyridyl is reported in a primate model of SAH. This result provides insight into the possible mechanism of delayed vasospasm after aneurysmal SAH and provides a potential preventive therapy for it.
Horky
L L
LL
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Pluta
R M
RM
Boock
R J
RJ
Oldfield
E H
EH
D015082:2,2'-Dipyridyl / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D002533:Cerebral Angiography; D005260:Female; D005296:Ferrous Compounds / Q000037:antagonists & inhibitors*; D007275:Injections, Intravenous; D007502:Iron Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000000981:diagnostic imaging / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008252:Macaca fascicularis; D008297:Male; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy*; D013997:Time Factors; D014168:Transferrin / Q000032:analysis
D005296:Ferrous Compounds; D007502:Iron Chelating Agents; D014168:Transferrin; D015082:2,2'-Dipyridyl